Is PCNT p.Arg9fs (c.25_34del) pathogenic?

PCNT p.Arg9fs (c.2534del) is classified Pathogenic in PCNT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). Very rare (popmax 8.48e-05%, nfe).

How common is PCNT p.Arg9fs (c.25_34del) in the general population?

PCNT p.Arg9fs (c.25_34del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PCNT p.Arg9fs

c.25_34del · rs2517836259 · VCV2842161

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 47
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,092 alleles

Overall 6.2e-05% 1/1,612,146 alleles · very rare exomes 1/1,459,804 · genomes 0/152,342 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PCNT
Protein: p.Arg9fs
Coding: c.25_34del
MANE Select: NM_006031
dbSNP: rs2517836259
Type: Deletion
Location: chr21:46324251 (GRCh38)
Gene constraint: LOEUF 0.943 · pLI <0.01 (gnomAD)
Residue 9: the 'disordered' region

Full PCNT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PCNT p.Arg9= Likely benign ★ same residue
PCNT c.2155-21_2186del Likely pathogenic ★★ same type
PCNT p.Ala995fs Pathogenic ★★ same type
PCNT p.Glu3290fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Gly1667fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.His203fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Leu1091fs Pathogenic/Likely pathogenic ★★ same type
PCNT p.Leu1910fs Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/pcnt-p-arg9fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown